Distinct Patterns of Evoked Firing in Engram and Non‐Engram Neurons in the Dentate Gyrus of Hippocampal Slices

Intense electrical activity modifies the cellular properties of neurons to enable the nervous system to store information. The dentate gyrus (DG) plays a role in learning and memory and its principal cell type, the granule cell (GC), can fire vigorously during behavior. To explore how experience modifies GC electrophysiology, we harnessed the immediate early gene, Fos, to target a genetically encoded hybrid voltage sensor to neurons that are activated by experience and are hypothesized to encode information. Voltage imaging from these engram GCs in mouse hippocampal slices revealed distinct patterns of stimulation-evoked spiking that depended on prior experience. Compared to unchallenged mice, engram GCs from mice exposed to novelty burst more often, and have longer inter-spike intervals following the blockade of inhibition. Voltage imaging from randomly targeted non-engram GCs revealed distinct firing patterns that did not depend on novelty. Thus, experience modifies the firing of both engram and non-engram GCs in distinctly different ways. The altered bursting will tune the facilitation of transmission from engram GCs to their various postsynaptic targets, and thus redirect the flow of information through the hippocampus. The pattern of GC firing constitutes a substrate for the encoding of information and will alter how the DG processes sensory inputs.